title: High-dose erythropoietin during cardiac resuscitation lessens postresuscitation myocardial stunning in swine.
abstract: We investigated the metabolic and functional myocardial effects of erythropoietin (EPO) administered during resuscitation from cardiac arrest using an open-chest pig model of ventricular fibrillation and resuscitation by extracorporeal circulation, after having reported in rats a reversal of postresuscitation myocardial dysfunction associated with activation of mitochondrial protective pathways. Ventricular fibrillation was induced in 16 male domestic pigs and left untreated for 8 minutes, after which extracorporeal circulation was started and maintained for 10 additional minutes, adjusting the extracorporeal flow to provide a coronary perfusion pressure of 10 mmHg. Defibrillation was accomplished and the extracorporeal flow was adjusted to secure a mean aortic pressure of 40 mmHg or greater during spontaneous circulation for up to 120 minutes. Pigs were randomized 1:1 to receive EPO (1200 U/kg) or 0.9% NaCl before starting extracorporeal circulation. Severe postresuscitation myocardial dysfunction developed in both groups. However, recovery of myocardial function-comparing baseline with 120 minutes postresuscitation-was better in pigs treated with EPO than NaCl, as shown for left ventricular ejection fraction (from 45 ± 8% to 36 ± 9% in EPO, not significant; and from 46 ± 8% to 26 ± 8% in NaCl, P < 0.001) and for peak systolic pressure/end-systolic volume (from 2.7 ± 0.8 mmHg/mL to 2.4 ± 0.7 mmHg/mL in EPO, not significant; and from 3.0 ± 1.1 mmHg/mL to 1.8 ± 0.6 mmHg/mL, P < 0.001 in NaCl). The EPO effect was associated with significantly higher myocardial O2 consumption (12 ± 6 mL/min/unit of tissue vs 6 ± 2 mL/min/unit of tissue, P < 0.017) without effects on myocardial lactate consumption. Thus, EPO administered during resuscitation from ventricular fibrillation lessened postresuscitation myocardial stunning-an effect that could be useful clinically to help promote postresuscitation hemodynamic stability.
authors.affiliation: Department of Medicine and Resuscitation Institute, Rosalind Franklin University of Medicine and Science, Ill.
authors.forename: Vesna
authors.initials: V
authors.lastname: Borovnik-Lesjak
authors.forename: Kasen
authors.initials: K
authors.lastname: Whitehouse
authors.forename: Alvin
authors.initials: A
authors.lastname: Baetiong
authors.forename: Bassel
authors.initials: B
authors.lastname: Artin
authors.forename: Jeejabai
authors.initials: J
authors.lastname: Radhakrishnan
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Gazmuri
mesh_terms: D000818:Animals; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D004554:Electric Countershock; D004921:Erythropoietin / Q000008:administration & dosage*; D005112:Extracorporeal Circulation; D006397:Hematinics / Q000008:administration & dosage*; D008297:Male; D017682:Myocardial Stunning / Q000503:physiopathology / Q000517:prevention & control*; D013552:Swine; D013997:Time Factors; D016896:Treatment Outcome; D014693:Ventricular Fibrillation / Q000503:physiopathology / Q000628:therapy*; D016277:Ventricular Function, Left
chemical_list: D006397:Hematinics; D004921:Erythropoietin
keywords: ADP; ATP; COX; CPP; CPR; ECC; EPO; LAD; LAD(RF); MVO(2); PKCε; VF; VF-EDD; adenosine diphosphate; adenosine triphosphate; cardiopulmonary resuscitation; coronary perfusion pressure; cytochrome c oxidase; eNOS; endothelial NO synthase; erythropoietin; extracorporeal circulation; left anterior descending coronary artery; myocardial O(2) consumption; protein kinase C epsilon; relative LAD blood flow; ventricular fibrillation; ventricular fibrillation while on extracorporeal circulation